We will continue studies on the biosynthesis of ergot alkaloids with the major focus on the following problems: (l) Sterochemistry and mechanism of the isoprenylation of tryptophan. (2) Enzymology of C- and D-ring closure of the ergoline system and of the formation of the peptide moiety of peptide ergot alkaloids. (3) Synthesis of potential intermediates in ergoline biosynthesis. (4) Mutant studies to obtain high-producing strains and to further unravel the biochemical and genetic control of alkaloid formation. The results are expected to ultimately help in the design of more efficient production methods for a class of compounds currently receiving considerable attention for their potential of yielding new useful drugs.